Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

Abstract

Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD 50 ) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae.

Dengue infection in mice inoculated by the intracerebral route: neuropathological effects and identification of target cells for virus replication

“…inoculation of a neuroadapted DENV2, strain New Guinea C (NGC), in BALB/c mice, which mimics some aspects of the viral encephalitis. This mouse model was previously used to test different vaccines against dengue 25–28 . Animals inoculated with the DENV2 presented morbidity, mainly hind leg paralysis and commitment of spinal cord, after the 7 th day post infection.…”

Immunovirotherapy Based on Recombinant Vesicular Stomatitis Virus: Where Are We?

“…Owing to their ability to prime robust humoral and cellular immunity, VSV vectors have also been used as vaccine agents to generate protective immunity against infections with highly lethal human viruses, including Ebola, HIV, Marburg, Lassa, Zika, and SARS-COV-2 viruses (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Other vaccine candidates using attenuated VSV vectors were evaluated in preclinical models to prevent illnesses due to influenza (41), hepatitis B virus (42), different strains of coronavirus causing respiratory diseases (43,44), Yersinia pestis (bubonic plague) (45), respiratory syncytial virus (RSV) (46), herpes simplex virus 2 (HSV2) (47), Dengue virus (48), Chikungunya virus (49), Nipah virus (50), and human papillomavirus (HPV) (51).…”

Self-replicating vehicles based on negative strand RNA viruses

“…VSV vectors have also been applied for DENV vaccine development. In this context, VSV expressing the DENV-2 pre-membrane (prM) and envelope (E) proteins was subcutaneously administered to BALB/c mice [49]. The immunization elicited anti-DENV-2 antibodies and protected mice against challenges with DENV-2.…”